PROJECT SUMMARY Obesity is a critical public health issue, and is responsible for a growing prevalence of diverse comorbidities that reduce quality of life and increase mortality risk. Obesity is an important risk factor for chronic kidney disease (CKD) and cardiovascular disease (CVD). Upregulation of the renin-angiotensin- aldosterone system, heightened sympathetic nervous system activity, vascular stiffness, and release of inflammatory cytokines contribute to the increased risk of CKD and CVD in obese patients. Accordingly, obesity is highly associated with the development of hypertension. As adiposity increases, patients are prone to glomerular hyperfiltration, amplified renal sodium reabsorption, extracellular volume overload, and impaired natriuresis. Thus, patients with excess adipose tissue are often more physiologically complex than lean hypertensive patients, and are at greater risk for many adverse outcomes related to hypertension. Nonetheless, little is known about appropriate blood pressure goals or the effects of specific antihypertensive agents on degree of blood pressure control in obese patients. The objective of the proposed studies is to better understand 1) if adiposity influences the effect of antihypertensive class on degree of BP control, and 2) the effect that degree of BP control has on the development and progression of CKD and CVD in obese, hypertensive patients. We will use prospective 24- hour ambulatory blood pressure monitoring in addition to longitudinal analyses of retrospective electronic health record data from two extremely largescale health systems, taking into account time-updated exposures and confounders. We will also use the electronic health record data to assess if there is a difference in initial antihypertensive class selection or BP threshold for initiation of antihypertensive treatment in obese versus non-obese patients. Using a multidisciplinary approach, we anticipate that this design will facilitate future optimization of medical management of patients with obesity and hypertension. I am currently funded by an NIH F32 grant, with board certification in Internal Medicine and Nephrology, and a Masters of Science in Clinical Epidemiology from the University of Pennsylvania. The K23 Career Development Award will enable me to develop research aimed at optimizing the pharmacologic management of the millions of obese, hypertensive patients living in the United States. My previous experience and training in longitudinal analyses have prepared me to engage in the work proposed in the studies, and will compliment my proposed intensive education in patient-oriented hypertension research, advanced longitudinal analytic techniques, pharmacoepidemiologic methods, and cardiovascular epidemiologic outcomes research. With the support of my highly experienced mentorship team and the ample resources available at the University of Pennsylvania?s Center for Clinical Epidemiology and Biostatistics, my goal is to foster a career of enduring research as an independent physician scientist, and to become a leader in the field of renal hypertension.